Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis

Susan Quinn De Joy, Robert Jeyaseelan, Lawrence W. Torley, Walter C. Pickett, Allan Wissner, Michael M. Wick, Arnold L. Oronsky, S. S. Kerwar

Research output: Contribution to journalArticle

Abstract

Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184, 005, a platelet-activating factor (PAF) antagonist. CL 184, 005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184, 005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184, 005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184, 005. Although TNF levels were significantly decreased in mice treated with CL 184, 005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184, 005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184, 005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalJournal of Infectious Diseases
Volume169
Issue number1
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Platelet Activating Factor
Staphylococcus aureus
Sepsis
Tumor Necrosis Factor-alpha
Enterotoxins
CL 184005
Nude Mice
Interleukin-6
Spleen
Hot Temperature
Blood Pressure
T-Lymphocytes
Serum

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology
  • Public Health, Environmental and Occupational Health

Cite this

Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis. / De Joy, Susan Quinn; Jeyaseelan, Robert; Torley, Lawrence W.; Pickett, Walter C.; Wissner, Allan; Wick, Michael M.; Oronsky, Arnold L.; Kerwar, S. S.

In: Journal of Infectious Diseases, Vol. 169, No. 1, 1994, p. 150-156.

Research output: Contribution to journalArticle

De Joy, SQ, Jeyaseelan, R, Torley, LW, Pickett, WC, Wissner, A, Wick, MM, Oronsky, AL & Kerwar, SS 1994, 'Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis', Journal of Infectious Diseases, vol. 169, no. 1, pp. 150-156. https://doi.org/10.1093/infdis/169.1.150
De Joy, Susan Quinn ; Jeyaseelan, Robert ; Torley, Lawrence W. ; Pickett, Walter C. ; Wissner, Allan ; Wick, Michael M. ; Oronsky, Arnold L. ; Kerwar, S. S. / Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis. In: Journal of Infectious Diseases. 1994 ; Vol. 169, No. 1. pp. 150-156.
@article{3ada7859ac4c4e18bcedabd687e765b3,
title = "Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis",
abstract = "Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184, 005, a platelet-activating factor (PAF) antagonist. CL 184, 005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184, 005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184, 005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184, 005. Although TNF levels were significantly decreased in mice treated with CL 184, 005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184, 005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184, 005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.",
author = "{De Joy}, {Susan Quinn} and Robert Jeyaseelan and Torley, {Lawrence W.} and Pickett, {Walter C.} and Allan Wissner and Wick, {Michael M.} and Oronsky, {Arnold L.} and Kerwar, {S. S.}",
year = "1994",
doi = "10.1093/infdis/169.1.150",
language = "English (US)",
volume = "169",
pages = "150--156",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis

AU - De Joy, Susan Quinn

AU - Jeyaseelan, Robert

AU - Torley, Lawrence W.

AU - Pickett, Walter C.

AU - Wissner, Allan

AU - Wick, Michael M.

AU - Oronsky, Arnold L.

AU - Kerwar, S. S.

PY - 1994

Y1 - 1994

N2 - Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184, 005, a platelet-activating factor (PAF) antagonist. CL 184, 005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184, 005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184, 005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184, 005. Although TNF levels were significantly decreased in mice treated with CL 184, 005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184, 005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184, 005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.

AB - Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184, 005, a platelet-activating factor (PAF) antagonist. CL 184, 005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184, 005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184, 005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184, 005. Although TNF levels were significantly decreased in mice treated with CL 184, 005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184, 005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184, 005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.

UR - http://www.scopus.com/inward/record.url?scp=0028147354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028147354&partnerID=8YFLogxK

U2 - 10.1093/infdis/169.1.150

DO - 10.1093/infdis/169.1.150

M3 - Article

C2 - 8277176

AN - SCOPUS:0028147354

VL - 169

SP - 150

EP - 156

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 1

ER -